150,000 Americans/yr suffer severe head injuries; 1/3 require anesthesia and surgery. Another 25-30,000 undergo anesthesia/surgery for intracranial tumors or vascular disorders. Such patients often need large amounts of intravenous fluid, either for resuscitation, replacement of intraoperative blood/fluid losses, or as therapy for ischemia. For the last 2+yrs, we have tried to examine the impact of these fluids on the brain, particularly the role of colloid oncotic pressure (COP), but experiments have demonstrated few differences between isotonic fluids and no effects of reducing COP on brain edema, intracranial pressure, EEG, or cerebral blood flow. This directly contradicts a widely held belief in the adverse effects of crystalloid solutions (e.g. lactated Ringer's). However, our work has focused on the period just after brain damage (<3 hrs), and delayed effects are possible (likely?). If continuation of support is awarded, we will try to determine if such delayed differences between crystalloids and colloids (e.g. hetastarch) exist, both when fluids are given acutely after injury (and brains examined 8 hrs later), and when administration is instituted approximately 24 hrs later, as occurs when patients are brought to the OR after a long delay. In addition, our attention has been drawn to a closely related area. The patients noted above also require anesthesia but while data exists the on effects of anesthetics on normal brain, our understanding of their effects on damaged brain is virtually nonexistent. We believe that anesthetics may act differently in the presence of brain injuries and that some anesthetics may alter the pathophysiologic progression of brain injury. We thus intend to ask 2 questions (which are reflected in the minor title change of this proposal): How does brain injury alter the cerebrovascular, metabolic, and electrophysiologic responses to anesthetics (compared with normal brain)? and Can anesthesia change the development of injury-induced changes in brain edema, ICP, etc.? It is hoped that all of these studies will improve our understanding of brain injury and anesthetic action, permit a more rational practice of neurosurgical anesthesia, and improve perioperative care of neurosurgical patients.